Chronic Kidney Disease
Conditions
Brief summary
The study goal is to assess the effect of senescent cell clearance on senescence burden, physical ability or frailty, and adipose tissue-derived mesenchymal stem cell (MSC) functionality in patients with chronic kidney disease (CKD).
Detailed description
The proposed studies will examine cellular senescence and the effect of senolytic therapy on senescent cell burden, frailty, and adipose-derived mesenchymal stem cell function in individuals with diabetic chronic kidney disease.
Interventions
Dasatinib - take one 100 mg tablet by mouth once daily for 3 consecutive days.
Quercetin - take four 250 mg capsules daily (total 1000 mg daily) for 3 consecutive days.
Sponsors
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Age 40-80 years 2. Chronic kidney disease estimated glomerular filtration rate (eGFR) 15-45 ml/min/1.73m2 3. Diabetes mellitus and taking diabetes medications
Exclusion criteria
1. Concomitant glomerulonephritis, 2. Nephrotic syndrome, 3. Solid organ transplantation, 4. Autosomal dominant or recessive polycystic kidney disease, 5. Known renovascular disease, 6. Pregnancy, 7. Active immunosuppression therapy, 8. Hemoglobin A1c≥10% at screening, 9. History of active substance abuse (including alcohol) within the past 2 years, 10. Current alcohol abuse (\>3 alcoholic beverages/day or \>21 per week), 11. Body weight \>150 kg or body mass index\>50 12. Human immunodeficiency virus infection 13. Active hepatitis B or C infection 14. Tyrosine kinase inhibitor therapy 15. Known hypersensitivity or allergy to dasatinib or quercetin 16. Inability to give informed consent 17. Uncontrolled systemic lupus erythematosus 18. Uncontrolled pleural/pericardial effusions or ascites 19. New invasive cancer except non-melanoma skin cancers 20. Invasive fungal or viral infection 21. Inability to tolerate oral medications 22. Total bilirubin\>2x upper limit of normal 23. Subjects taking medications that are sensitive to substrates or substrates with a narrow therapeutic range for CYP3A4, CYP2C8, CYP2C9, or CYP2D6 or strong inhibitors or inducers of CYP3A4 (e.g. cyclosporine, tacrolimus or sirolimus). If antifungals are absolutely necessary from an infectious disease perspective, then they will be allowed only if the levels are therapeutic. 24. Subjects on strong inhibitors of CYP3A4. 25. Subjects on therapeutic doses of anticoagulants (Warfarin (Coumadin);Rivaroxaban (Xarleto); Apixaban (Eliquis); Dabigatran (Pradaxa, Prazaxa) or Other). 26. Subjects on antiplatelet agents ((Clopidogrel (Plavix); Dipyridamole + Asprin (Aggrenox); Ticagrelor (Brilinta); Prasugrel (Effient); Ticlopidine (Ticlid) or Other) who are unable or unwilling to reduce or hold therapy prior to and during the 3-day drug dosing. Subjects may continue their previous regimen on day 4. 27. Subjects on quinolone antibiotic therapy for treatment or for prevention of infections within 10 days 28. Subjects taking H2-antagonists or proton pump inhibitors and unwilling to discontinue therapy 1 week prior and 2 weeks following enrollment. 29. Corrected QT interval (QTc)\>450 msec 30. Presence of any condition that the Investigator believes would put the subject at risk or would preclude the patient from successfully completing all aspects of the trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in proportion of senescent cells (representing the total senescent cell burden) present | Baseline, Day 14 | Assessment of senescence markers in skin, fat, and/or blood at baseline and day 14. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in proportion of senescent mesenchymal stem cells present | Baseline, Day 14 | Assessment of senescence markers in mesenchymal stem cells at baseline and day 14. |
| Change in mesenchymal stem cell function | Baseline, Day 14 | Assessment of functional studies in mesenchymal stem cells at baseline and day 14. Number of subjects with change in stem cell function related to treatment. |
| Change in Frailty index score | Baseline, Day 14 | Assessment by Fried and other frailty criteria at baseline and day 14. |
| Change in kidney function | Baseline, Day 14, Month 4, Month 12 | Assessment by estimated and measured glomerular filtration rate at baseline, day 14, month 4, and month 12. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORLaTonya J Hickson, MD
Mayo Clinic
Outcome results
None listed